One of the major impediments to immunizing the world's children with a protective course of vaccinations against childhood diseases is the requirement for a complex course of booster immunizations. It has become clear that a significant proportion of this target population does not complete the full immunization regimen because of the number of clinic visits required. The primary goal of this proposal is to develop microencapsulated formulations of the current diphtheria, acellular pertussis, tetanus and Haemophilus influenza type B vaccines which will replace the pediatric vaccination series with a single injection at 2 months of age. The vaccines will be individually microencapsulated in poly(DL-lactide-co-glycolide)(DL- PLG), a biodegradable and biocompatible polyester which is approved for human use. Our studies have shown that the delivery of protein and glycoprotein-based vaccines in DL-PLG microspheres strongly potentiates antibody responses. The antibody responses in mice to the microencapsulated vaccines will be measured by ELISA, and the protective efficacy of the responses tested in in vitro neutralization and bactericidal assays and in in vivo protection from lethal challenge studies. The biodegradation rate of DL-PLGs is determined by the ratio of lactide-to-glycolide in the copolymers. Thus, Vaccine-microspheres with different DL-PLGs release at different times after injection, and may be co-injected to deliver discrete pulses of vaccine which function as primary and booster immunizations. Each of the vaccines will be encapsulated in a series of DL-PLGs designed to release vaccine pulses which mimic the current 2, 4, 6 and 15-19 month immunization schedule after a single injection. The single injection pulse-release mixture of microencapsulated vaccines will be evaluated for appropriate booster responses, protective efficacy, absence of vaccine cross interference and stability with time and increased temperature.